In 1981, Weinreb and Nahm obtained ketones by adding lithium or magnesium organometallics to N-methyl-N-methoxyamides.
Weinreb's amides are prepared from acid halides or anhydrides by reaction with N,O-dimethylhydroxylamine in the presence of base (pyridine).
![weinreb synthesis 01](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-01.png)
![weinreb synthesis 02](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-02.png)
Weinreb's amide can be reduced with DIBAL yielding the corresponding aldehyde.
![weinreb synthesis 03](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-03.png)
It is also possible to obtain Weinreb's amide from esters and lactones, catalyzing the reaction with a Lewis acid such as trimethylaluminium.
![weinreb synthesis 04](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-04.png)
Mechanism:
Amide formation:
![weinreb synthesis 05](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-05.png)
Reaction with organometallic:
![weinreb synthesis 06](/images/stories/reacciones-organicas/weinreb-sintesis-cetonas/weinreb-sintesis-06.png)